The objective of this project is to acquire new knowledge about the role of the CD8 T cells in protectingagainst influenza infection. The CD8 T cell response is thought to play a pivotal role in clearinginfection and establishing protective immunity from studies in animal models. However, thequantitative and qualitative characteristics of the influenza A virus-specific CD8 T cell response tonatural infection and vaccines have not been investigated systematically in the human host. Wepropose to evaluate influenza A virus-specific CD8 T cells in child populations and adults. Experimentswill use multi-color flow cytometry-based techniques which overcome technical obstacles to assessingCD8 T cell immunity in human populations, including children, to characterize CD8 T cells specific forinfluenza A antigens. Prospective evaluations will be done in all age cohorts who are immunized withinactivated or live attenuated influenza vaccines and in children with natural influenza A infection.
The Specific Aims are: 1. To characterize the influenza A-specific CD8 T cell response before and afteradministration of inactivated influenza vaccine or live attenuated influenza vaccine to children, youngadults, and older adults. We hypothesize that immunization will induce effector and memory CD8 T cellresponses at different time points, as characterized by specific patterns of multiple phenotypes and Tcell functions. We expect responses to differ by vaccine type, and age. 2. To characterize the number,phenotype and functions of influenza A virus-specific effector and memory CD8 T cells in children withacute influenza. To evaluate antiviral CD8 T cell responses in children allows study of the primary CD8T cell response in naTve exposed, subjects. We hypothesize that CD8 T cell responses induced bynatural infection will resemble responses to live vaccine. This project is a component of our coordinatedefforts addressing T cell and B cell responses as well as natural killer responses to influenza A usingthe same cohort of human subjects and will provide new information on the CD8 T cell immunity in thecontext of the overall host responses to influenza A. This information will be critical for providingenhanced protection during a potential influenza A pandemic while it is naturally occurring or abioterrorist event.
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